Splitting probabilities as a test of reaction coordinate choice in single-molecule experiments

TL;DR

This paper proposes using splitting probabilities as a straightforward method to evaluate the suitability of reaction coordinates in single-molecule experiments, demonstrated through DNA hairpin force spectroscopy data.

Contribution

It introduces a novel test based on splitting probabilities to assess reaction coordinate choices in biomolecular single-molecule experiments.

Findings

Splitting probability comparison can reject unsuitable reaction coordinates.

The method is demonstrated on DNA hairpin force spectroscopy data.

Provides a simple, model-based test for reaction coordinate validation.

Abstract

To explain the observed dynamics in equilibrium single-molecule measurements of biomolecules, the experimental observable is often chosen as a putative reaction coordinate along which kinetic behavior is presumed to be governed by diffusive dynamics. Here, we invoke the splitting probability as a test of the suitability of such a proposed reaction coordinate. Comparison of the observed splitting probability with that computed from the kinetic model provides a simple test to reject poor reaction coordinates. We demonstrate this test for a force spectroscopy measurement of a DNA hairpin.